Developmental regulation of the intracellular Ca2+ sensitivity of vesicle fusion and Ca2+-secretion coupling at the rat calyx of Held
Developmental regulation of the intracellular Ca2+ sensitivity of vesicle fusion and Ca2+-secretion coupling at the rat calyx of Held
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DOI：
10.1113/jphysiol.2009.172387
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发表时间：
2009-06-15
影响因子：
5.5
通讯作者：
Schneggenburger, Ralf
中科院分区：
文献类型：
--
作者：
Kochubey, Olexiy;Han, Yunyun;Schneggenburger, Ralf
突触传递的发育细化可以通过几种突触前和突触后因素的变化来实现，但尚不清楚神经末梢囊泡融合的内在Ca2+敏感性是否可以在发育过程中受到调节。利用听觉通路中的巨大突触 Held 花萼，我们研究了 Ca2+ 分泌耦合发育调节的突触前机制，比较了大鼠听力出现之前和之后不久的时间段。我们发现 EPSC 幅度和突触前 Ca2+ 电流电荷 (Q(Ca)) 之间的关系存在类似 2 倍的左移，表明短暂的突触前 Ca2+ 电流在驱动释放方面变得显着更有效。使用 Ca2+ 尾电流方案，我们还发现 EPSC 振幅和 Q(Ca) 之间的高协同性随着发育而略有降低。相反，在突触前 Ca2+ 释放实验中，囊泡融合的内在 Ca2+ 协同性是相同的，并且内在 Ca2+ 敏感性随着发育而略有降低。这表明短暂 Ca2+ 电流释放效率的显着增强一定是由 Ca2+ 通道和易于释放的囊泡更紧密的共定位引起的，而不是由 Ca2+ 依赖性释放的内在特性的变化引起的。使用在每个发育阶段测量的内在 Ca2+ 敏感性参数，我们估计在突触前动作电位 (AP) 期间，给定的易于释放的囊泡在发育过程中会经历约 1.3 倍高的“局部”细胞内 Ca2+ 浓度 ([Ca2+](i)) 信号。因此，数据表明在发育过程中 Ca2+ 通道-囊泡共定位收紧，而囊泡融合的内在 Ca2+ 敏感性没有重大变化。
Developmental refinement of synaptic transmission can occur via changes in several pre- and postsynaptic factors, but it has been unknown whether the intrinsic Ca2+ sensitivity of vesicle fusion in the nerve terminal can be regulated during development. Using the calyx of Held, a giant synapse in the auditory pathway, we studied the presynaptic mechanisms underlying the developmental regulation of Ca2+-secretion coupling, comparing a time period before, and shortly after the onset of hearing in rats. We found an similar to 2-fold leftward shift in the relationship between EPSC amplitude and presynaptic Ca2+ current charge (Q(Ca)), indicating that brief presynaptic Ca2+ currents become significantly more efficient in driving release. Using a Ca2+ tail current protocol, we also found that the high cooperativity between EPSC amplitude and Q(Ca) was slightly reduced with development. In contrast, in presynaptic Ca2+ uncaging experiments, the intrinsic Ca2+ cooperativity of vesicle fusion was identical, and the intrinsic Ca2+ sensitivity was slightly reduced with development. This indicates that the significantly enhanced release efficiency of brief Ca2+ currents must be caused by a tighter co-localization of Ca2+ channels and readily releasable vesicles, but not by changes in the intrinsic properties of Ca2+-dependent release. Using the parameters of the intrinsic Ca2+ sensitivity measured at each developmental stage, we estimate that during a presynaptic action potential (AP), a given readily releasable vesicle experiences an about 1.3-fold higher 'local' intracellular Ca2+ concentration ([Ca2+](i)) signal with development. Thus, the data indicate a tightening in the Ca2+ channel-vesicle co-localization during development, without a major change in the intrinsic Ca2+ sensitivity of vesicle fusion.